Expansive intervention as neo-institutional learning:root causes in the Merida Initiative

Interventions since the 1990s have greatly expanded in policy scope. While neo-liberals understand expansion as an attempt to work on the enabling preconditions of liberal market democracy, Foucauldian governmentality studies see in expansion a set of increasingly intrusive disciplinary techniques of responsibilization. This paper introduces an alternative lens: neo-institutional learning. Through a case study of the Merida Initiative, a US–Mexican security cooperation agreement, the paper argues that expansion grows serendipitously out of the repetitive discovery of new, ‘deeper’ unknowns within a neo-institutional framework of analysis. Importantly, downward penetration requires deconstructing reductionist liberal-universal knowledge claims. Paradoxically, then, the more statebuilders learn (empirically), the less they know (analytically)

A descriptive analysis of child-relevant systematic reviews in the Cochrane Database of Systematic Reviews

Background: Systematic reviews (SRs) are considered an important tool for decision-making. There has been no recent comprehensive identification or description of child-relevant SRs. A description of existing child-relevant SRs would help to identify the extent of available child-relevant evidence available in SRs and gaps in the evidence base where SRs are required. The objective of this study was to describe child-relevant SRs from the Cochrane Database of Systematic Reviews (CDSR, Issue 2, 2009).Methods: SRs were assessed for relevance using pre-defined criteria. Data were extracted and entered into an electronic form. Univariate analyses were performed to describe the SRs overall and by topic area.Results: The search yielded 1666 SRs; 793 met the inclusion criteria. 38% of SRs were last assessed as up-to-date prior to 2007. Corresponding authors were most often from the UK (41%). Most SRs (59%) examined pharmacological interventions. 53% had at least one external source of funding. SRs included a median of 7 studies (IQR 3, 15) and 679 participants (IQR 179, 2833). Of all studies, 48% included only children, and 27% only adults. 94% of studies were published in peer-reviewed journals. Primary outcomes were specified in 72% of SRs. Allocation concealment and the Jadad scale were used in 97% and 25% of SRs, respectively. Adults and children were analyzed separately in 12% of SRs and as a subgroup analysis in 14%. Publication bias was assessed in only 14% of SRs. A meta-analysis was conducted in 68% of SRs with a median of 5 trials (IQR 3, 9) each. Variations in these characteristics were observed across topic areas.Conclusions: We described the methodological characteristics and rigour of child-relevant reviews in the CDSR. Many SRs are not up-to-date according to Cochrane criteria. Our study describes variation in conduct and reporting across SRs and reveals clinicians' ability to access child-specific data

A descriptive analysis of child-relevant systematic reviews in the Cochrane Database of Systematic Reviews

<p>Abstract</p> <p>Background</p> <p>Systematic reviews (SRs) are considered an important tool for decision-making. There has been no recent comprehensive identification or description of child-relevant SRs. A description of existing child-relevant SRs would help to identify the extent of available child-relevant evidence available in SRs and gaps in the evidence base where SRs are required. The objective of this study was to describe child-relevant SRs from the Cochrane Database of Systematic Reviews (CDSR, Issue 2, 2009).</p> <p>Methods</p> <p>SRs were assessed for relevance using pre-defined criteria. Data were extracted and entered into an electronic form. Univariate analyses were performed to describe the SRs overall and by topic area.</p> <p>Results</p> <p>The search yielded 1666 SRs; 793 met the inclusion criteria. 38% of SRs were last assessed as up-to-date prior to 2007. Corresponding authors were most often from the UK (41%). Most SRs (59%) examined pharmacological interventions. 53% had at least one external source of funding. SRs included a median of 7 studies (IQR 3, 15) and 679 participants (IQR 179, 2833). Of all studies, 48% included only children, and 27% only adults. 94% of studies were published in peer-reviewed journals. Primary outcomes were specified in 72% of SRs. Allocation concealment and the Jadad scale were used in 97% and 25% of SRs, respectively. Adults and children were analyzed separately in 12% of SRs and as a subgroup analysis in 14%. Publication bias was assessed in only 14% of SRs. A meta-analysis was conducted in 68% of SRs with a median of 5 trials (IQR 3, 9) each. Variations in these characteristics were observed across topic areas.</p> <p>Conclusions</p> <p>We described the methodological characteristics and rigour of child-relevant reviews in the CDSR. Many SRs are not up-to-date according to Cochrane criteria. Our study describes variation in conduct and reporting across SRs and reveals clinicians' ability to access child-specific data.</p

The impact of plasma protein binding on the renal transport of organic anions

ABSTRACT Drugs and xenobiotics bind to plasma proteins with varying degrees of affinity, and the amount of binding has a direct effect on free drug concentration and subsequent pharmacokinetics. Multiple active and facilitative transport systems regulate the excretion of anionic compounds from the blood in excretory and barrier tissues. Assumptions are made about in vivo substrate affinity and route of elimination based on data from plasma protein-free in vitro assays, particularly following expression of cloned transporters. Ochratoxin A (OTA), a fungal mycotoxin, is a high-affinity substrate for several renal secretory organic anion transporters (OATs), and literature suggests that this elimination pathway is the route of entry leading to proximal tubule-targeted toxicity. However, OTA is known to bind to several plasma proteins with a high affinity, particularly serum albumin, which may impact elimination. In this study, we have systematically examined the handling of OTA and other organic anions, estrone sulfate (ES) and methotrexate (MTX), by OATs in the presence of serum albumin. Increasing concentrations of albumin markedly reduced uptake of OTA by both Xenopus laevis oocytes expressing OATs 1, 3, and 4 and organic anion-transporting polypeptide 1. For all transporters tested, virtually all mediated OTA uptake was eliminated by an albumin concentration equivalent to 10% of that present in the blood plasma. Thus, OTA uptake is dependent on the free substrate concentration and severely limited by binding to human serum albumin. MTX and ES uptake were likewise dependent on free concentration. The proximal tubule is the primary site for renal secretory elimination of drugs, toxins, and their metabolites from the body. In addition, the proximal tubule exhibits a very high metabolic demand since it mediates not only secretion of drugs and xenobiotics but also the reabsorption of 60 to 80% of the solute and water filtered by the glomerulus Elimination of drugs, toxins, and their metabolites is handled by several facilitative and active epithelial transport proteins expressed in the proximal tubule. Since the advent of cloning and the extensive study of these transporters in vitro, the impact of plasma protein has generally been overlooked when predicting physiological roles of transporters in the renal elimination of drugs. Nevertheless, plasma proteins are abundant, and the potential for altered transporter efficacy is substantial. For example, serum albumin, a major transport/carrier plasma protein [4% (w/v)], makes up approximately 60% of total plasma protein Certainly, the impact of binding will vary depending upon the affinity of plasma proteins for the drug of interest. The organic anion, p-aminohippuric acid (PAH), provides an example of a substrate impacted minimally by plasma protein binding. It binds with low affinity to albumin [binding constant (K b ) ϳ 2.3 ϫ 10 3 M Ϫ1